Infectious Hepatitis C Virus Pseudo-particles Containing Functional E1–E2 Envelope Protein Complexes

By B. Bartosch, J. Dubuisson, F. Cosset. Journal of Experimental Medicine, 2003

1,209 citations recorded by the source corpus.

The study of hepatitis C virus (HCV), a major cause of chronic liver disease, has been hampered by the lack of a cell culture system supporting its replication. Here, we have successfully generated infectious pseudo-particles that were assembled by displaying unmodified and functional HCV glycoproteins onto retroviral and lentiviral core particles. The presence of a green fluorescent protein marker gene packaged within these HCV pseudo-particles allowed reliable and fast determination of infectivity mediated by the HCV glycoproteins. Primary hepatocytes as well as hepato-carcinoma cells were found to be the major targets of infection in vitro. High infectivity of the pseudo-particles required both E1 and E2 HCV glycoproteins, and was neutralized by sera from HCV-infected patients and by some anti-E2 monoclonal antibodies. In addition, these pseudo-particles allowed investigation of the role of putative HCV receptors. Although our results tend to confirm their involvement, they provide evidence that neither LDLr nor CD81 is sufficient to mediate HCV cell entry. Altogether, these studies indicate that these pseudo-particles may mimic the early infection steps of parental HCV and will be suitable for the development of much needed new antiviral therapies.

Subfields: Epidemiology, Hepatology, Radiology, Nuclear Medicine and Imaging

View Paper: https://www.semanticscholar.org/paper/08198e5322918c50418687d3448914e8e88ec8c9

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Citations in the corpus

Immunobiology and pathogenesis of viral hepatitis. (2006, background): “Furthermore, antibodies specific for HCV E1 and E2 glycoproteins can block the infection of susceptible cells with pseudotyped lentiviral vectors expressing these envelope proteins (45, 50, 51).”
Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinct sites (2009, methodology): “Pseudotyped virions were produced essentially as described previously (30), with plasmids for pseudotyping kindly provided by Jean Dubuisson (Lille Pasteur Institute, Lille, France).”
Murine Leukemia Virus (MLV)-based Coronavirus Spike-pseudotyped Particle Production and Infection (2016, methodology): “Transfection plasmids and reagents a. Plasmids pCMV-MLVgag-pol (ampicillin resistance) (Bartosch et al., 2003) b. pTG-Luc (ampicillin resistance) (Bartosch et al., 2003) c. pCAGGS-MERS-S (ampicillin resistance) (Millet and Whittaker, 2014) d. pCAGGS-VSV-G (ampicillin resistance) e. pCAGGS…”
Human occludin is a hepatitis C virus entry factor required for infection of mouse cells (2009, methodology): “Pseudoparticles were generated by FuGENE6 (Roche Applied Science)-mediated cotransfection of 293T cells with plasmids encoding (1) a minimal HIV (pTRIP, CSGW, CSPW) or MLV (LMN8) provirus encoding green fluorescent protein (GFP) or other transgene; (2) gag-pol (HIV or MLV); and (3) appropriate viral”
Hepatitis C Virus Entry Depends on Clathrin-Mediated Endocytosis (2006, methodology): “A first advance has been the production of infectious retroviral particles pseudotyped with HCV envelope glycoproteins (3, 14, 24).”
SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies (2021, positive): “, 2018) or pQCXIP_ACE2 expression vectors in combination with plasmids coding for VSV-G and MLV-Gag/Pol (Bartosch et al., 2003).”
Replication of hepatitis C virus (2007, background): “, pseudoparticles (engineered retroviral particles bearing functional HCV envelope proteins) that enable the study of viral entry under reproducible and conveniently measurable condition”
Production of infectious hepatitis C virus in tissue culture from a cloned viral genome (2005, positive): “Neutralization of HCV infection by CD81-specific antibody CD81 was shown to be involved in HCV entry using HCV pseudoparticle”
Immunology of hepatitis B virus and hepatitis C virus infection (2005, neutral): “, infection of hepatoma cells with HCV PSEUDOTYPE PARTICLES”